In order to increase the precision with which individual patients are treated with NSAID's we propose to test the hypothesis that there is a body fluid drug concentration versus clinical efficacy relationship for several of these drugs. We will attempt to use pharmacokinetic parameters established in a given individual to enable us to predict the dose of drug needed to achieve therapeutic drug levels in that individual, thus optimizing his therapy. By constructing utility indices, we will attempt to establish a method to compare the various NSAID's, thus establishing the relative order in which these durgs may best be used. Both total and unbound drug concentrations will be measured. For NSAID's with a long half-life (e.g. naproxen) and relatively stable plateau drug concentrations, correlation of total and free plateau serum may be sufficient. For tolmetin, with a short serum half-life, a number of pharmacokinetic parameters using total and free serum concentrations, and synovial fluid levels will be analyzed in correlations with efficacy. Similarly, spinal fluid and serum "free" salicylate levels and pH will be examined in patients with salicylate overdoses to determine whether they correlated better than serum total drug levels with the patient's clinical status and outcome.